Fetal Lung-Derived Exosomes in Term Labor Amniotic Fluid Induce Amniotic Membrane Senescence

Shuting Wan; Pengzheng Chen; Mengqi Gu; Jing Liu; Qian Zhou; Fengyuan Zhang; Yuan Lu; Lei Li; Xietong Wang

doi:10.3389/fcell.2022.889861

Fetal Lung-Derived Exosomes in Term Labor Amniotic Fluid Induce Amniotic Membrane Senescence

Front Cell Dev Biol. 2022 Jul 4:10:889861. doi: 10.3389/fcell.2022.889861. eCollection 2022.

Authors

Shuting Wan¹, Pengzheng Chen¹, Mengqi Gu¹, Jing Liu¹, Qian Zhou¹, Fengyuan Zhang², Yuan Lu¹, Lei Li^{1

2

3}, Xietong Wang^{1

2

3

4

5}

Affiliations

¹ Department of Obstetrics and Gynaecology, Shandong Provincial Hospital Affiliated with Shandong University, Jinan, China.
² Department of Obstetrics and Gynaecology, Shandong Provincial Hospital Affiliated with Shandong First Medical University, Jinan, China.
³ The Laboratory of Medical Science and Technology Innovation Center (Institute of Translational Medicine), Shandong First Medical University (Shandong Academy of Medical Sciences) of China, Jinan, China.
⁴ Department of Obstetrics and Gynaecology, Maternal and Child Health Care of Shandong Province, Jinan, China.
⁵ The Laboratory of Placenta-Related Diseases, Key Laboratory of Birth Regulation and Control Technology of the National Health and Family Planning Commission of China, Jinan, China.

Abstract

The mechanism of parturition is still unclear. Evidence has shown that delivery is associated with cellular senescence of the amniotic membrane. We isolated fetal lung-associated exosomes from the amniotic fluid from term labor (TL-exos) and verified that the exosomes can cause primary human amniotic epithelial cell (hAEC) senescence and apoptosis and can release higher levels of senescence-associated secretory phenotype (SASP)-related molecules and proinflammatory damage-associated molecular patterns (DAMPs) than exosomes isolated from the amniotic fluid from term not in labor (TNIL-exos). The human lung carcinoma cell lines (A549) can be used as an alternative to alveolar type 2 epithelial cells producing pulmonary surfactant. Therefore, we isolated A549 cell-derived exosomes (A549-exos) and found that they can trigger hAEC to undergo the same aging process. Finally, the animal experiments suggested that A549-exos induced vaginal bleeding and preterm labor in pregnant mice. Therefore, we conclude that exosomes derived from fetal lungs in term labor amniotic fluid induce amniotic membrane senescence, which may provide new insight into the mechanism of delivery.

Keywords: exosome; fetal lung; inflammation; parturition; senescence.